Creutzfeldt-Jakob disease, a subacute spongiform virus encephalopathy of man, has been serially transmitted to guinea pigs. The pathogenesis, routes of inoculation, infectivity determinations and evolution of the morphological lesions as seen with light and electron microscopy will be determined in timed experiments in this animal model. Infectivity of subcellular fractions from infected tissues will be monitored and the site and physical and chemical characteristics of the agent will be examined. Further concentration of the agent will be attempted using various chemical techniques such as affinity chromatography on lectin-sepharose columns. Tissue culture of infected brain will be utilized for possible propagation of the agent and its further characterization. Spingoglycolipid changes in brain of experimentally transmitted Creutzfeldt-Jakob disease in guinea pigs will be studied. Such changes will be assessed in correlation with the histopathological findings in these brains.